Schmidt Stanislaw, Tramsen Lars, Schneider Andreas, Schubert Ralf, Balan Ada, Degistirici Özer, Meisel Roland, Lehrnbecher Thomas
Divisions for Pediatric Hematology and Oncology, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, Frankfurt, Germany.
Divisions for Pediatric Pulmonology, Allergology and Cystic Fibrosis, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, Frankfurt, Germany.
Oncotarget. 2017 Sep 8;8(56):95495-95503. doi: 10.18632/oncotarget.20753. eCollection 2017 Nov 10.
Mesenchymal stromal cells (MSCs) are increasingly given as immunotherapy to hematopoietic stem cell transplant (HSCT) recipients with refractory graft-versus-host disease (GvHD). Whereas the immunosuppressive properties of MSCs seem to be beneficial in GvHD, there is, at the same time, major concern that MSCs increase the risk for infection. We therefore investigated the interplay of human MSCs with and the impact of MSCs on different arms of the anti- host response . Although hyphae increase mRNA levels of in MSCs, the extracellular availability of IL-6 and other pro-inflammatory cytokines remains unaffected. Human MSCs are able to phagocyte conidia, but phagocytosis of conidia is not associated with an alteration of the cytokine production by MSCs. In addition, human MSCs do not affect activation and function of specific CD4 T cells, and MSCs do not negatively impact the oxidative burst activity of phagocytes. Our data indicate that administration of human MSCs is not associated with a negative impact on the host response against and that the fungus does not stimulate MSCs to increase the release of those cytokines which play a central role in the pathophysiology of GvHD.
间充质基质细胞(MSCs)越来越多地被用作免疫疗法,用于治疗患有难治性移植物抗宿主病(GvHD)的造血干细胞移植(HSCT)受者。虽然MSCs的免疫抑制特性似乎对GvHD有益,但与此同时,人们主要担心MSCs会增加感染风险。因此,我们研究了人MSCs与抗宿主反应不同环节之间的相互作用以及MSCs对其的影响。尽管菌丝增加了MSCs中白细胞介素-6(IL-6)的mRNA水平,但IL-6和其他促炎细胞因子的细胞外可用性仍未受影响。人MSCs能够吞噬烟曲霉分生孢子,但分生孢子的吞噬作用与MSCs细胞因子产生的改变无关。此外,人MSCs不影响特异性CD4 T细胞的激活和功能,并且MSCs对吞噬细胞的氧化爆发活性没有负面影响。我们的数据表明,给予人MSCs对宿主抗烟曲霉反应没有负面影响,并且该真菌不会刺激MSCs增加那些在GvHD病理生理学中起核心作用的细胞因子的释放。